期刊
CANCER CELL
卷 25, 期 6, 页码 809-821出版社
CELL PRESS
DOI: 10.1016/j.ccr.2014.04.026
关键词
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资金
- OHSU Department of Dermatology Molecular Profiling Resource (IRB) [809]
- OHSU Knight Cancer Institute [NCI P30CA069533]
- American Association for Cancer Research
- NIH [T32 CA108462]
- Department of Defense Breast Cancer Research Program Fellowship [W81XWH-09-1-0543]
- NIH/NCI [T32CA106195, T32A107890304, R01 CA130980, R01 CA140943, R01 CA155331, U54 CA163123]
- DOD BCRP Era of Hope Scholar Expansion Award [W81XWH-08-PRMRP-IIRA]
- Susan B Komen Foundation [KG111084, KG110560]
- Breast Cancer Research Foundation
- Rigel Pharmaceuticals
B cells foster squamous cell carcinoma (SCC) development through deposition of immunoglobulin-containing immune complexes in premalignant tissue and Fc gamma receptor-dependent activation of myeloid cells. Because human SCCs of the vulva and head and neck exhibited hallmarks of B cell infiltration, we examined B cell-deficient mice and found reduced support for SCC growth. Although ineffective as a single agent, treatment of mice bearing preexisting SCCs with B cell-depleting alpha CD20 monoclonal antibodies improved response to platinum- and Taxol-based chemotherapy. Improved chemoresponsiveness was dependent on altered chemokine expression by macrophages that promoted tumor infiltration of activated CD8(+) lymphocytes via CCR5-dependent mechanisms. These data reveal that B cells, and the downstream myeloid-based pathways they regulate, represent tractable targets for anticancer therapy in select tumors.
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